Statistical cure, defined as achieving life expectancy comparable with that of disease-free individuals, has not been specifically investigated in hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC), which accounts for more than 50% of the global HCC burden. This study aimed to develop a cure model for HBV-HCC after hepatectomy using matched HBV carriers and the general population as reference groups.

From a Chinese multicenter database, HBV-HCC patients who underwent curative-intent hepatectomy were retrospectively reviewed. Independent prognostic factors were identified through Cox regression. A spline-based cure model was applied using two reference populations: matched Chinese HBV carriers (from Shanghai Center for Disease Control and Prevention) and the general population (from the National Bureau of Statistics).

The study analyzed 740 HBV-HCC patients. The following eight independent risk factors were identified: preoperative high viral load (hazard ratio [HR] 1.27), Child-Pugh grade (HR 1.21 and 1.43), multiple tumors (HR 1.70), tumor size greater than 5.0 cm (HR 1.47), macrovascular invasion (HR 3.33), microvascular invasion (HR 1.25), intraoperative blood transfusion (HR 1.21), and postoperative HBV reactivation (HR 1.89). The overall cure probability was 21.2% versus that for HBV carriers and 11.1% versus that for the general population. Risk stratification identified distinct groups relative to HBV carriers. Low risk (64.2%) showed an initial cure rate of 30.3% and achieved a 95% cure probability by 8.6 years, whereas high risk (10.5%) showed negligible cure probability.

This first HBV-HCC-specific cure model demonstrated that statistical cure is achievable for a subset of patients after hepatectomy. Risk stratification identifies patients with varying cure probabilities, providing valuable guidance for personalized treatment strategies and surveillance protocols.

Despite advances in surgical treatment, high recurrence after surgery remains a challenge for patients with hepatocellular carcinoma (HCC). This study aimed to investigate the association between compliance to regular follow-up and long-term oncological outcomes among patients undergoing curative resection for HCC.

This multicenter study included patients who underwent curative resection for early-stage HCC between January 2012 and December 2021 at 12 liver surgery centers. Patients were stratified into a regular follow-up group (follow-up every 2-3 months for the first 2 years and every 3-6 months thereafter) and an irregular/no follow-up group. Overall survival (OS), time to recurrence (TTR), and post-recurrence survival (PRS) were compared between the two groups.

Among 1544 patients, 786 (50.9%) underwent regular follow-up during postoperative follow-up. The regular follow-up group had better OS (median: 113.4 vs. 94.5 months, P = 0.010) and PRS (median: 37.9 vs. 16.3 months, P < 0.001) than the irregular/no follow-up group, although TTR was comparable (median: 61.4 vs. 66.2 months, P = 0.161). Furthermore, patients in the regular follow-up group had a lower incidence of tumor beyond the Milan criteria at recurrence (41.6% vs. 50.4%, P = 0.013) and were more likely to receive curative treatments for recurrence (56.1% vs. 49.3%, P = 0.061). On multivariate analysis, compliance to regular follow-up was an independent factor associated with better OS [hazard ratio (HR) = 0.777, 95% confidence interval (CI): 0.663-0.910, P = 0.002] and PRS (HR = 0.523, 95% CI: 0.428-0.638, P < 0.001).

Compliance to regular follow-up improved OS and PRS after curative resection for HCC, highlighting the importance of postoperative regular follow-up for early detection of recurrence and timely intervention.

Distant metastasis after hepatectomy for hepatocellular carcinoma (HCC) significantly impairs long-term outcome. This study aimed to identify patterns, risk factors, and develop a prediction model for distant metastasis at first recurrence following HCC resection. This multi-center retrospective study included patients undergoing curative hepatectomy for HCC. Risk factors for distant metastasis were identified using Cox regression. A nomogram was constructed and validated using the concordance index (C-index) and calibration curves. Among 2,705 patients, 1,507 experienced recurrence, with 342 (22.7 per cent) developing distant metastasis. Common metastatic sites included extrahepatic vessels (36.2 per cent), lungs (26.0 per cent), and lymph nodes (20.8 per cent). Patients with distant metastasis had significantly worse 5-year overall survival compared to those with intrahepatic recurrence (9.1 versus 41.1 per cent, p < 0.001). Independent risk factors included preoperative tumor rupture, tumor size over 5.0 cm, multiple tumors, satellite nodules, macro- and microvascular invasion, narrow resection margin, and intraoperative blood transfusion. The nomogram demonstrated excellent discrimination (C-index > 0.85) and accurately stratified patients into three risk categories. In conclusion, distant metastasis at first recurrence following HCC resection was associated with poor prognosis. The proposed nomogram facilitates accurate prediction of distant metastasis, potentially informing personalized postoperative monitoring and interventions for high-risk patients.

The ASAP score, which incorporates age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence-II, has demonstrated promise for early detection of hepatocellular carcinoma (HCC). However, its prognostic value after HCC treatment remains unknown. The current study sought to evaluate the prognostic value of the ASAP score to predict recurrence and survival following curative hepatic resection for HCC.

This study using prospectively collected data included HCC patients who underwent curative-intent hepatic resection. The ASAP score was calculated preoperatively, and X-tile analysis was used to determine the optimal cutoff value. Univariate and multivariate analyses were performed to identify independent risk factors associated with recurrence and overall survival (OS).

Among 1239 patients in the analytic cohort, the optimal ASAP score cutoff was 4.8; patients were divided into low (n = 749) and high (n = 490) ASAP score subgroups. Patients with high ASAP scores had a higher incidence of 5-year recurrence (73.9% vs 51.0%, P < 0.001) and worse OS (31.7% vs 60.1%, P < 0.001) versus individuals with low scores. Multivariate analysis identified ASAP score ≥4.8 as an independent risk factor of both recurrence (hazard ratio [HR] 1.976, 95% confidence interval [CI]: 1.633-2.390, P < 0.001) and OS (HR 1.407, 95% CI 1.170-1.691, P < 0.001) after controlling for established clinicopathological factors.

Preoperative ASAP score was independently associated with recurrence and survival after HCC resection. The clinical utility of the ASAP score may be applicable to both diagnosis and prognosis, potentially improving postoperative surveillance and management strategies for HCC patients.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

Our study aimed to combine the morphological behavior (tumor burden score, TBS) and the biological behavior (AFP and PIVKA-II) to predict the prognosis of HCC patients after radical liver resection.

A total of 1766 HCC patients were divided into the training cohort (n = 1079) and the validation cohort (n = 687) with a ratio of 6:4. The Kaplan-Meier method was used to analyze the recurrence-free (RFS) and overall survival (OS). The multivariable Cox regression model was established based on the variables screened by the least absolute shrinkage and selection operator (LASSO) regression to identify variables independently associated with recurrence-free survival (RFS) and overall survival (OS). Constructing our prognostic score (TBS-LN(AFP + PIVKA-II) score, TAP score) based on regression coefficients and the predictive ability of the TAP score was compared with Barcelona Clinic Liver Cancer (BCLC) stage.

The TAP score had good performance in stratifying RFS (p < 0.001) and OS (p < 0.001) in the training cohort and the validation cohort. There still existed significant differences in the intergroup comparisons among three TAP score groups for RFS and OS in the training cohort and the validation cohort. In our LASSO-Cox regression model, the TAP score was independently associated with RFS and OS. The TAP score also outperformed the BCLC stage in predicting RFS (1, 2 and 3 years) and OS (1, 3 and 5 years).

The TAP score had good performance in predicting the prognosis of HCC patients after radical liver resection and was superior to the BCLC stage.

Patients with hepatocellular carcinoma (HCC) who undergo curative hepatectomy may experience varying remnant liver volumes. Our study aimed to evaluate whether the extent of liver resection has an effect on postoperative recurrence in HCC patients at China Liver Cancer Staging (CNLC) Ib stage.

A retrospective analysis was conducted on 197 patients who underwent hepatectomy for a solitary HCC lesion measuring ≥5 cm (CNLC Ιb stage) between January 2019 and June 2022. Patients were divided into a major hepatectomy (MAH) group ( n =70) and a minor hepatectomy (MIH) group ( n =127) based on the extent of liver resection. Recurrence-free survival (RFS) was compared between the two groups. Propensity score matching (PSM) was employed to minimize bias in the retrospective analysis.

Patients who underwent MAH had a greater total complication rate than those who underwent MIH (35.7 vs. 11.8%, P <0.001). The median RFS was 14.6 months (95% CI: 11.1-18.1) for the MAH group and 24.1 months (95% CI: 21.2-27.1) for the MIH group ( P <0.001). After PSM, patients who underwent MAH still had a greater total complication rate than those who underwent MIH (36.7 vs. 16.3%, P =0.037). The median RFS was 13.2 months (95% CI: 15.1-21.7) for the MAH group and 22.3 months (95% CI: 18.1-26.5) for the MIH group ( P =0.0013). The Cox regression model identified MAH as an independent poor predictor for HCC recurrence (hazard ratios of 1.826 and 2.062 before and after PSM, respectively; both P <0.05).

MIH can be performed with fewer postoperative complications and contributes to improved RFS in patients with HCC at CNLC Ιb stage compared to MAH. Parenchyma-sparing resection should be considered the first choice for these HCCs.

The growing demand for surgical resection in elderly patients with hepatocellular carcinoma highlights the need to understand the impact of preoperative frailty on surgical outcomes. The aim of this multicentre cohort study was to investigate the association between frailty and short- and long-term outcomes after hepatic resection among elderly patients with hepatocellular carcinoma.

A multicentre analysis was conducted on elderly patients with hepatocellular carcinoma (aged greater than or equal to 70 years) who underwent curative-intent resection at ten Chinese hospitals from 2012 to 2021. Frailty was assessed using the Clinical Frailty Scale (with frailty defined as a Clinical Frailty Scale score greater than or equal to 5). The primary outcomes were overall survival and recurrence-free survival; secondary outcomes encompassed postoperative 30-day morbidity and mortality, and 90-day mortality. The outcomes between patients with and without preoperative frailty were compared.

Of the 488 elderly patients, 148 (30.3%) were considered frail. Frail patients experienced significantly higher 30-day morbidity (68.9% (102 of 148) versus 43.2% (147 of 340)), 30-day mortality (4.1% (6 of 148) versus 0.6% (2 of 340)), and 90-day mortality (6.1% (9 of 148) versus 0.9% (3 of 340)) compared with non-frail patients (all P < 0.010). During a median follow-up of 37.7 (interquartile range 20.4-57.8) months, frail patients demonstrated significantly worse median overall survival (41.6 (95% c.i. 32.0 to 51.2) versus 69.7 (95% c.i. 55.6 to 83.8) months) and recurrence-free survival (27.6 (95% c.i. 23.1 to 32.1) versus 42.7 (95% c.i. 34.6 to 50.8) months) compared with non-frail patients (both P < 0.010). Multivariable Cox regression analysis revealed frailty as an independent risk factor for decreased overall survival (HR 1.61; P = 0.001) and decreased recurrence-free survival (HR 1.32; P = 0.028).

Frailty is significantly associated with adverse short-term and long-term outcomes after resection in elderly patients with hepatocellular carcinoma. The findings suggest that frailty assessment should be incorporated into perioperative and postoperative evaluation for elderly patients undergoing hepatocellular carcinoma resection.

Hepatocellular carcinoma (HCC) exhibits a propensity for early recurrence following liver resection, resulting in a bleak prognosis. At present, majority of the predictive models for the early postoperative recurrence of HCC rely on the linear assumption of the Cox Proportional Hazard (CPH) model. However, the predictive efficacy of this model is constrained by the intricate nature of clinical data. The present study aims to investigate the efficacy of the random survival forest (RSF) model, which is a machine learning algorithm, in predicting the early postoperative recurrence of HCC, and compare its performance with that of the traditional CPH model. This analysis seeks to elucidate the potential advantages of the RSF model over the CPH model in addressing this clinical challenge.

The present retrospective cohort study was conducted at a single center. After excluding 41 patients, a total of 541 patients were included in the final model construction and subsequent analysis. The patients were randomly divided into two groups at a 7:3 ratio: training group (n = 378) and validation group (n = 163). The least absolute shrinkage and selection operator (LASSO) regression was used to identify the risk factors in the training group. Then, the identified factors were used to develop the RSF and CPH regression models. The predictive ability of the model was assessed using the concordance index (C-index). The accuracy of the model predictions was evaluated using the receiver operating characteristic curve (ROC) and area under the receiver operating characteristic curve (AUC). The clinical practicality of the model was measured by decision curve analysis (DCA), and the overall performance of the model was evaluated using the Brier score. The RSF model was visually represented using the Shapley additive explanations (SHAP) framework. Then, the RSF, CPH regression, and albumin-bilirubin (ALBI) grade models were compared.

The following variables were examined by LASSO regression: alpha fetoprotein (AFP), gamma-glutamyl transpeptidase to platelet ratio (GPR), blood transfusion (BT), microvascular invasion (MVI), large vessel invasion (LVI), Edmondson-Steiner (ES) grade, liver capsule invasion (LCI), satellite nodule (SN), and Barcelona clinic liver cancer (BCLC) grade. Then, a RSF model was developed using 500 trees, and the variable importance (VIMP) ranking was MVI, LCI, SN, BT, BCLC, ESG, AFP, GPR and LVI. After these aforementioned factors were applied, the RSF and CPH regression models were developed and compared using the ALBI grade model. The C-index for the RSF model (0.896 and 0.798, respectively) outperformed that of the CPH regression model (0.803 and 0.772, respectively) and ALBI grade model (0.517 and 0.515, respectively), in both the training and validation groups. Three time points were selected to assess the predictive capabilities of these models: 6, 12 and 18 months. For the training group, the AUC value for the RSF model at 6, 12 and 18 months was 0.971 (95% CI: 0.955-0.988), 0.919 (95% CI: 0.887-0.951) and 0.899 (95% CI: 0.867-0.932), respectively. For the validation cohort, the AUC value for the RSF model at 6, 12 and 18 months was 0.830 (95% CI: 0.728-0.932), 0.856 (95% CI: 0.787-0.924) and 0.832 (95% CI: 0.764-0.901), respectively. The AUC values were higher in the RSF model, when compared to the CPH regression model and ALBI grade model, in both groups. The DCA results revealed that the net clinical benefits associated to the RSF model were superior to those associated to the CPH regression model and ALBI grade model in both groups, suggesting a higher level of clinical utility in the RSF model. The Brier score for the RSF model at 6, 12 and 18 months was 0.062, 0.125 and 0.178, respectively, in the training group, and 0.111, 0.128 and 0.149, respectively, in the validation group. In summary, the RSF model demonstrated superior performance, when compared to the CPH regression model and ALBI grade model. Furthermore, the RSF model demonstrated superior predictive ability, accuracy, clinical practicality, and overall performance, when compared to the CPH regression model and ALBI grade model. In addition, the RSF model was able to successfully stratify patients into three distinct risk groups (low-risk, medium-risk and high-risk) in both groups (p < 0.001).

The RSF model demonstrates efficacy in predicting early recurrence following HCC surgery, exhibiting superior performance, when compared to the CPH regression model and ALBI grade model. For patients undergoing HCC surgery, the RSF model can serve as a valuable tool for clinicians to postoperatively stratify patients into distinct risk categories, offering guidance for subsequent follow-up care.

Bone mineral density (BMD) and monocyte-to-lymphocyte ratio (MLR) were recently identified as novel risk factors for patients with several malignancies. The objective of this study was to validate the role of preoperative BMD/MLR as a potential prognostic biomarker in patients with hepatocellular carcinoma (HCC) undergoing liver resection.

This investigation enrolled 442 adult patients diagnosed with HCC who underwent liver resection. The patients were classified into high- and low-BMD/MLR groups based on the median, and forward stepwise logistic regression was employed to identify independent predictors for early HCC recurrence. To mitigate the impact of confounding factors, a propensity score matching (PSM) analysis was conducted between patients in the high- and low-BMD/MLR groups. The Kaplan-Meier method was employed to assess and compare the disease-free survival (DFS) and overall survival (OS) between the two cohorts.

The study categorized patients into high-BMD/MLR and low-BMD/MLR groups. Forward stepwise logistic regression analysis revealed that low BMD/MLR (P < 0.001), tumor size > 50 mm (P < 0.001), and AFP > 200 ug/L (P = 0.001) were significantly associated with the early recurrence of HCC. Moreover, the results suggested that DFS and OS were significantly shorter in the low-BMD/MLR group compared to the high-BMD/MLR group, both before and after PSM (P < 0.05).

Preoperative BMD/MLR held promise as a prognostic biomarker for early recurrence and prognosis in patients with HCC who underwent liver resection. Furthermore, the integration of tumor size, AFP level, and BMD/MLR demonstrated a robust predictive capacity for early recurrence within this patient population.

This study examines the relationship between tumor burden score (TBS) and survival and recurrence following radical resection of hepatocellular carcinoma through a cohort study conducted in the Guangxi population of China.

This cohort study eventually recruited 576 HCC patients undergoing radical resection of HCC in the People's Hospital of Guangxi Zhuang Autonomous Region during 2013-2022. After determining the best threshold TBS, all cases were grouped to evaluate the relationship between TBS versus overall survival (OS) and cumulative recurrence. Using X-Tile software, the best threshold TBS to judge patient prognostic outcome following radical resection of HCC was 10.77.

Kaplan-Meier curve analysis revealed that patients with high TBS showed considerably decreased OS relative to the control group, accompanied by an increased recurrence rate. According to multivariate Cox proportional regression, the patients with high TBS were associated with poorer OS (HR = 2.56, 95% CI 1.64-3.99, P < 0.001) and recurrence-free survival (RFS) (HR = 1.55, 95% CI 1.02-2.35, P < 0.001).

In patients undergoing radical resection for HCC, higher TBS was significantly related to shorter OS and RFS.

Both subcutaneous adipose tissue (SAT) and neutrophil-to-lymphocyte ratio (NLR) are associated with the prognosis of hepatocellular carcinoma (HCC). Subcutaneous adipose tissue is an immunonutritional indicator, and NLR reflects the inflammatory status. The purpose of this study was to ascertain the validity of SAT/NLR as potential prognostic biomarkers in HCC patients who are undergoing liver resection.

This retrospective study encompassed the sequential enrollment of 682 patients diagnosed with HCC who underwent liver resection. The patients were categorized into high and low SAT/NLR groups using the median value, and forward stepwise logistic regression was utilized to ascertain independent predictors for one-year HCC recurrence. In order to minimize the influence of confounding variables, a propensity score matching (PSM) analysis was conducted between patients in high and low SAT/NLR groups. The Kaplan-Meier method was employed to assess and compare the recurrence-free survival (RFS) and overall survival (OS) between the two groups.

The study divided patients into two groups based on their SAT/NLR levels: high SAT/NLR (≥35.34) and low SAT/NLR (<35.34) groups. Forward stepwise logistic regression analysis revealed that low SAT/NLR (p < 0.001), tumor size ≥50 mm (p < 0.001), alpha-fetoprotein level >200 ng/mL (p < 0.001), and presence of liver cirrhosis (p < 0.001) were significantly associated with one-year recurrence of HCC. Moreover, the results suggest that RFS and OS were significantly shorter in the low SAT/NLR group compared to the high SAT/NLR group, both before and after PSM (p < 0.05).

The preoperative biomarker SAT/NLR shows potential as a prognostic biomarker for one-year recurrence and prognosis in patients with HCC undergoing liver resection.

Objective.In oncology, clinical decision-making relies on a multitude of data modalities, including histopathological, radiological, and clinical factors. Despite the emergence of computer-aided multimodal decision-making systems for predicting hepatocellular carcinoma (HCC) recurrence post-hepatectomy, existing models often employ simplistic feature-level concatenation, leading to redundancy and suboptimal performance. Moreover, these models frequently lack effective integration with clinically relevant data and encounter challenges in integrating diverse scales and dimensions, as well as incorporating the liver background, which holds clinical significance but has been previously overlooked.Approach.To address these limitations, we propose two approaches. Firstly, we introduce the tensor fusion method to our model, which offers distinct advantages in handling multi-scale and multi-dimensional data fusion, potentially enhancing overall performance. Secondly, we pioneer the consideration of the liver background's impact, integrating it into the feature extraction process using a deep learning segmentation-based algorithm. This innovative inclusion aligns the model more closely with real-world clinical scenarios, as the liver background may contain crucial information related to postoperative recurrence.Main results.We collected radiomics (MRI) and histopathological images from 176 cases diagnosed by experienced clinicians across two independent centers. Our proposed network underwent training and 5-fold cross-validation on this dataset before validation on an external test dataset comprising 40 cases. Ultimately, our model demonstrated outstanding performance in predicting early recurrence of HCC postoperatively, achieving an AUC of 0.883.Significance.These findings signify significant progress in addressing challenges related to multimodal data fusion and hold promise for more accurate clinical outcome predictions. In this study, we exploited global 3D liver background into modelling which is crucial to to the prognosis assessment and analyzed the whole liver background in addition to the tumor region. Both MRI images and histopathological images of HCC were fused at high-dimensional feature space using tensor techniques to solve cross-scale data integration issue.

Unresectable recurrence after curative treatments for hepatocellular carcinoma (HCC) is a life-limited event. Although the IMbrave050 trial (IM050) showed a favorable reduction in recurrence with adjuvant immune-combination chemotherapy, inclusion criteria of the radiofrequency ablation (RFA) group were lower risk than that of the resection group. This study aimed to elucidate the clinical features of patients treated with RFA, which really need adjuvant-chemotherapy.

From 2000 to 2022, 528 patients with Child-Pugh A and HCC within the Milan criteria (MC), who met the IM050 criteria for RFA and undergone resection or RFA, were enrolled (71 years, HCV:HBV:HBV/HCV:alcohol:others = 337:44:5:53:89, multi-tumor = 138, RFA:resection = 309:219). Unresectable recurrence was defined as beyond the MC. Risk factors for recurrence beyond the MC were retrospectively evaluated.

Multivariate Cox-hazard analysis showed HCV-positive (HR 1.49), AFP-L3 > 10% (HR 1.75), and DCP > 100 mAU/mL (HR1.80) as significant prognostic factors for recurrence beyond the MC (each P < 0.05). Summing of positive factors (1 point for each) was used for scoring (AD-ON score), which showed increased positive rates for micro-hepatic vein invasion (score 0:1:2:3 = 0%:1.1%:6.6%:15.8%), micro-portal vein invasion (0:1:2:3 = 2.0%:12.1%:14.1%:31.6%), and poor differentiation (0:1:2:3 = 6.0%:6.7%:15.3%:15.8%) in the resection group associated with a greater score (each P < 0.01). In patients treated with RFA, those with greater AD-ON scores showed shorter time to recurrence beyond the MC, recurrence-free time, and overall survival (score 0:1:2:3 = no-estimation:97:66:23 months, 35:27:20:12 months, and 91:82:67:52 months, respectively, each P < 0.05).

HCC patients treated by RFA and with a high AD-ON score (≧2) should be considered for aggressive adjuvant-chemotherapy to prolong the period of recurrence beyond the MC.

This study aims to investigate the predictive value of Gadobenate dimeglumine (Gd-BOPTA) enhanced MRI features on microvascular invasion (MVI) and recurrence in patients with Liver Imaging Reporting and Data System (LI-RADS) category 5 hepatocellular carcinoma (HCC).

A total of 132 patients with LI-RADS category 5 HCC who underwent curative resection and Gd-BOPTA enhanced MRI at our hospital between January 2016 and December 2018 were retrospectively analyzed. Qualitative evaluation based on LI-RADS v2018 imaging features was performed. Logistic regression analyses were conducted to assess the predictive significance of these features for MVI, and the Cox proportional hazards model was used to identify postoperative risk factors of recurrence. The recurrence-free survival (RFS) was analyzed by using the Kaplan-Meier curve and Log rank test.

Multivariate logistic regression analysis identified that corona enhancement (odds ratio [OR] = 3.217; p < 0.001), internal arteries (OR = 4.147; p = 0.004), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR = 5.165; p < 0.001) were significantly associated with MVI. Among the 132 patients with LR-5 HCC, 62 patients experienced postoperative recurrence. Multivariate Cox regression analysis showed that mosaic architecture (hazard ratio [HR] = 1.982; p = 0.014), corona enhancement (HR = 1.783; p = 0.039), and peritumoral hypointensity on HBP (HR = 2.130; p = 0.009) were risk factors for poor RFS.

MRI features based on Gd-BOPTA can be noninvasively and effectively predict MVI and recurrence of LR-5 HCC patients.

To explore factors associated with overall survival (OS) and progression-free survival (PFS) of intrahepatic cholangiocarcinoma (iCCA) after ultrasound-guided ablation and establish a model for survival risk evaluation.

Data from 54 patients with 86 iCCAs between August 2008 and October 2022 were retrospectively analyzed. Cox regression were used to analyze the effects of clinical features on OS and PFS. Based on the variables screened by multivariable analysis, a model was established to predict the survival of the patients. Time-dependent receiver operating characteristic (timeROC) curve was constructed to evaluate the performance of this model. The model was further verified by bootstrap validation. The clinical usefulness of the model was evaluated by the decision curve analysis (DCA).

During follow up, 39 patients died and 49 patients developed recurrence. Pre-ablation CA199 level > 140 U/ml was the only independent predictor of poor PFS. Age > 70 years, early recurrence, maximal diameter of tumor size > 1.5 cm and pre-ablation CA199 level > 140 U/ml were significantly associated with poor OS. Then a model was established based on the above four variables. The areas under the timeROC curve (AUC) for 1-year, 2-year, 3-year, 5-year were 0.767, 0.854, 0.791 and 0.848, respectively. After bootstrapping for 1000 repetitions, the AUCs were similar to the initial model. DCA also demonstrated that the model had good positive net benefits.

The established model in this study could predict the survival outcomes of the patients with iCCA after thermal ablation, but further research was needed to validate the results.

Hepatocellular carcinoma (HCC) stands as the most prevalent form of primary liver cancer and is highly invasive and easily recurs. For HCC, chemotherapy shows limited effect. The gold standard for HCC treatment includes curative surgical resection or liver transplantation. However, the recurrence rate at 5 years after liver resection is estimated at approximately 70% and even at 5 years after liver transplantation, it is 20%. Therefore, improving survival outcomes after curative surgical resection of liver cancer is crucial. This review highlights the importance of identifying risk factors for HCC recurrence following radical surgical resection and adjuvant therapy options that may reduce the recurrence risk and improve overall survival, including local adjuvant therapy (e.g., transcatheter arterial chemoembolization and radiotherapy), adjuvant systemic therapy (e.g., small molecule targeted therapy and immunotherapy), and other adjuvant therapies (e.g., chemotherapy). However, further research is needed to refine the use of these therapies and optimize their effectiveness in preventing HCC recurrence.

Chaihu Shugan San (CSS) is a well-known traditional herbal formula that has the potential to ameliorate hepatocellular carcinoma (HCC); however, its mechanism of action remains unknown. Here, we identified the key targets of CSS against HCC and developed a prognostic model to predict the survival of patients with HCC. The effect of CSS plus sorafenib on HCC cell proliferation was evaluated using the MTT assay. LASSO-Cox regression was used to establish a three-gene signature model targeting CSS. Correlations between immune cells, immune checkpoints and risk score were determined to evaluate the immune-related effects of CSS. The interactions between the components and targets were validated using molecular docking and Surface Plasmon Resonance (SPR) assays. CSS and sorafenib synergistically inhibited HCC cell proliferation. Ten core compounds and 224 targets were identified using a drug compound-target network. The prognostic model of the three CSS targets (AKT1, MAPK3 and CASP3) showed predictive ability. Risk scores positively correlated with cancer-promoting immune cells and high expression of immune checkpoint proteins. Molecular docking and SPR analyses confirmed the strong binding affinities of the active components and the target genes. Western blot analysis confirmed the synergistic effect of CSS and sorafenib in inhibiting the expression of these three targets. In conclusion, CSS may regulate the activity of immune-related factors in the tumour microenvironment, reverse immune escape, enhance immune responses through AKT1, MAPK3, and CASP3, and synergistically alleviate HCC. The co-administration of sorafenib with CSS has a strong clinical outlook against HCC.

According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, tumor burden and liver function, but not tumor biology, are the key factors in determining tumor staging and treatment modality, and evaluating treatment prognosis. The serum α-fetoprotein (AFP) level is an important characteristic of hepatocellular carcinoma (HCC) biology, and we aimed to evaluate its prognostic value for patients undergoing liver resection of early-stage HCC.

Patients who underwent curative liver resection for early-stage HCC were identified from a multi-institutional database. Patients were divided into three groups according to preoperative AFP levels: low (< 400 ng/mL), high (400-999 ng/mL), and extremely-high (≥ 1000 ng/mL) AFP groups. Overall survival (OS) and recurrence rates were compared among these three groups.

Among 1284 patients, 720 (56.1%), 262 (20.4%), and 302 (23.5%) patients had preoperative low, high, and extremely-high AFP levels, respectively. The cumulative 5-year OS and recurrence rates were 71.3 and 38.9% among patients in the low AFP group, 66.3 and 48.5% in the high AFP group, and 45.7 and 67.2% in the extremely-high AFP group, respectively (both p < 0.001). Multivariate Cox regression analysis identified both high and extremely-high AFP levels to be independent risk factors of OS (hazard ratio [HR] 1.275 and 1.978, 95% confidence interval [CI] 1.004-1.620 and 1.588-2.464, respectively; p = 0.047 and p < 0.001, respectively) and recurrence (HR 1.290 and 2.050, 95% CI 1.047-1.588 and 1.692-2.484, respectively; p = 0.017 and p < 0.001, respectively).

This study demonstrated the important prognostic value of preoperative AFP levels among patients undergoing resection for early-stage HCC. Incorporating AFP to prognostic estimation of the BCLC algorithm can help guide individualized risk stratification and identify neoadjuvant/adjuvant treatment necessity.

In Germany, organ allocation is based on the MELD-system and lab-MELD is usually low in patients with hepatocellular carcinoma (HCC) in cirrhosis. Higher medical urgency can be achieved by standard exception for HCC (SE-HCC), if Milan criteria (MC) are met. Noteworthy, UNOS T2 reflects MC, but excludes singular lesions < 2 cm. Thus, SE-HCC is awarded to patients with one lesion between 2 and 5 cm or 2 to 3 lesions between 1 and 3 cm. These criteria are static and do not reflect biological properties of HCC.We present a retrospective cohort of 111 patients, who underwent liver transplantation at UKSH, Campus Kiel between 2007 and 2017. No difference was found in overall survival for patient cohorts using Milan, UCSF, up-to-seven, and French-AFP criteria. However, there was a significantly reduced survival, if microvascular invasion was detected in the explanted organ and in patients with HCC-recurrence. The exclusive use of static selection criteria including MC appear to limit the access to liver transplantation.

Tumor morphology links to early recurrence of hepatocellular carcinoma. Controversy exists regarding the recurrence risk of Liver Imaging Reporting and Data System morphologic Type II hepatocellular carcinoma. This study aims to explore risk factors for early recurrence of Type II hepatocellular carcinoma.

Retrospective analysis of hepatocellular carcinoma patients who underwent curative resection and preoperative contrast-enhanced MRI from June 2016 to June 2020. Our patients formed the development set, and hepatocellular carcinoma patients from the TCIA database served as validation. Univariable and multivariable Cox regression identified independent risk factors for early recurrence. A risk scoring system was established for risk stratification, and an early recurrence prediction model was developed and validated.

95 Type II hepatocellular carcinoma patients were in the development set, and 29 cases were in the validation set. Early recurrence rates were 33.7% and 37.9%, respectively. Multivariate analysis revealed age, histological grade, AFP, and intratumoral hemorrhage as independent risk factors for early recurrence. The model's diagnostic performance for early recurrence was AUC = 0.817 in the development set. A scoring system classified patients into low-risk (scores ≤ 3) and high-risk (scores > 3) groups. The high-risk group had significantly lower recurrence-free survival (40.0% vs 73.2%, P = 0.001), consistent with the validation set (25.0% vs 73.3%, P = 0.028).

The risk scoring system demonstrated excellent discrimination and predictive ability, aiding clinicians in assessing early recurrence risk and identifying high-risk individuals effectively.

No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma.

In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098.

The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab.

Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully.

F Hoffmann-La Roche/Genentech.

The prevention of recurrence for patients with hepatocellular carcinoma after curative resection is still a great challenge in clinical practice. There are numerous studies that trying to search for favorable strategies to decrease the recurrence and prolong life span for these patients, whereas no consensus is reached till now. Herein, we aim to compare the efficacy between different reported treatments by network meta-analysis(NMA).

We searched Pubmed, Web of Science and Cochrane Library for abstracts and full-text articles published from database inception through February 2023. All of the random controlled trials(RCTs) were evaluated and collected as eligible studies. The primary outcome was the prevention of recurrence between different procedures. The second outcomes were one-year survival, three-year survival and five-year survival.

Thirty-two RCTs including 5783 patients were selected, and 12 treatments were classified. Most of the studies were high quality with low bias. Thirty-one studies including 5629 patients were recruited for recurrence analysis. The network meta-analysis showed benefits from transarterial chemoembolization(TACE) + portal vein chemotherapy(PVC)[OR, 2.84 (1.15,6.99)] and internal radiotherapy(IRT) [OR, 2.63 (1.41,4.91)] compared to non-adjuvant(NA) treatment when considering prevention of recurrence. Seventeen studies including 2047 patients were collected for one-year survival analysis. The network meta-analysis showed benefit from TACE[OR, 0.33 (0.14,0.75)] when considering one-year survival. Twenty-one studies including 2463 patients were collected for three-year survival analysis. The network meta-analysis showed TACE [OR, 0.51 (0.30,0.86)], IRT[OR, 0.41 (0.20,0.83)] and dendritic cell(DC) [OR, 0.09 (0.01,0.98)] were better than NA when considering three-year survival. Sixteen studies including 1915 patients were collected for five-year survival analysis. The network meta-analysis didn't show any benefit from different treatments when considering five-year survival. Other strategies including external radiotherapy(ERT), branched-chain amino acids(BCAA), hepatic artery infusion chemotherapy(HAIC), cytokine-induced killer(CIK), adoptive immunotherapy(AIT), Huaier, interferon(IFN), oral chemotherapy(OCT) and sorafenib(SOR) didn't show significant benefit regardless of prevention of recurrence or short-, long- time survival.

This NMA found that TACE + PVC and IRT were considered as the procedures to decrease HCC recurrence rate. TACE, IRT and DC were preferred when considering the extending of life span for post-operative patients with HCC. Large scale of RCTs are needed to verify it.

This study aimed to develop a noninvasive predictive model for identifying early postoperative recurrence of hepatocellular carcinoma (within 2 years after surgery) based on contrast-enhanced ultrasound and serum biomarkers. Additionally, the model's validity was assessedthrough internal and external validation. Clinical data were collected from patients who underwent liver resection at the First Hospital of Quanzhou and Mengchao Hepatobiliary Hospital. The data included general information, contrast-enhanced ultrasound parameters, Liver Imaging Reporting and Data System (LI-RADS) classification, and serum biomarkers. The data from Mengchao Hospital were divided into 2 groups, with a ratio of 6:4, to form the modeling and internal validation sets, respectively. On the other hand, the data from the First Hospital of Quanzhou served as the external validation group. The developed model was named the Hepatocellular Carcinoma Early Recurrence (HCC-ER) prediction model. The predictive efficiency of the HCC-ER model was compared with other established models. The baseline characteristics were found to be well-balanced across the modeling, internal validation, and external validation groups. Among the independent risk factors identified for early recurrence, LI-RADS classification, alpha-fetoprotein, and tumor maximum diameter exhibited hazard ratios of 1.352, 1.337, and 1.135 respectively. Regarding predictive accuracy, the HCC-ER, Tumour-Node-Metastasis, Barcelona Clinic Liver Cancer, and China Liver Cancer models demonstrated prediction errors of 0.196, 0.204, 0.201, and 0.200 in the modeling group; 0.215, 0.215, 0.218, and 0.212 in the internal validation group; 0.210, 0.215, 0.216, and 0.221 in the external validation group. Using the HCC-ER model, risk scores were calculated for all patients, and a cutoff value of 50 was selected. This cutoff effectively distinguished the high-risk recurrence group from the low-risk recurrence group in the modeling, internal validation, and external validation groups. However, the calibration curve of the predictive model slightly overestimated the risk of recurrence. The HCC-ER model developed in this study demonstrated high accuracy in predicting early recurrence within 2 years after hepatectomy. It provides valuable information for developing precise treatment strategies in clinical practice and holds considerable promise for further clinical implementation.

This meta-analysis was dedicated to evaluating the safety and effectiveness of indocyanine green (ICG) -mediated fluorescence molecular imaging (FMI) technology in liver tumors resection.

A literature search of PubMed, Embase databases, Cochrane Library, and Web of Science was performed to identify all clinical controlled studies exploring the effects of fluorescence imaging on liver tumors resection. Quality assessment and data extraction of studies were conducted independently by 3 reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software.

14 retrospective cohort studies (RCSs) involving a total of 1227 patients were finally included. The results showed that Fluorescence-assisted liver tumors resection could improve the R0 resection rate (OR = 2.63; 95% CI: 1.46~4.73, p = 0.001), reduce overall complications (OR = 0.66; 95% CI: 0.44~0.97, p = 0.04), biliary fistula (OR = 0.20; 95% CI: 0.05~0.77, p = 0.02), intraoperative blood loss (MD = -70.76, 95% CI: -106.11 to -35.41; p < 0.0001), and shortens hospital stay (MD = -1.41, 95% CI: -1.90 to -0.92; p < 0.00001). There were no significant differences in the incidences of operative time (MD = -8.68, 95% CI: -18.59 to -1.22; p = 0.09), complications of grade III or above (OR = 0.73; 95% CI: 0.43~1.25, p = 0.26), liver failure (OR = 0.86; 95% CI: 0.39~1.89, p = 0.71), and blood transfusion (OR = 0.66; 95% CI: 0.42~1.03, p = 0.07).

Current evidence suggests that ICG-mediated FMI technology could enhance the clinical effectiveness of patients with liver tumors resection and is clinically worthy of promotion.

PROSPERO, identifier CRD42022368387.

Currently used treatment algorithms were originally established based on the clinical outcomes of the initial treatment for primary hepatocellular carcinoma (HCC), and no strong evidence exists yet to suggest if these algorithms could also be applicable to patients with recurrent HCC after surgery. As such, this study sought to explore an optimal risk stratification method for cases of recurrent HCC for better clinical management.

Among the 1616 patients who underwent curative resection for HCC, the clinical features and survival outcomes of 983 patients who developed recurrence were examined in detail.

Multivariate analysis confirmed that both the disease-free interval (DFI) from the previous surgery and tumor stage at recurrence were significant prognostic factors. However, the prognostic impact of DFI seemed different according to the tumor stages at recurrence. While curative-intent treatment showed strong influence on survival [hazard ratio (HR), 0.61; P < 0.001] regardless of the DFI in patients with stage 0 or stage A disease at recurrence, early recurrence (< 6 months) was a poor prognostic marker in patients with stage B disease. The prognosis of patients with stage C disease was exclusively influenced by the tumor distribution or choice of treatment than by the DFI.

The DFI complementarily predicts the oncological behavior of recurrent HCC, with its predictive value differing depending on the tumor stage at recurrence. These factors should be considered for selection of the optimal treatment in patients with recurrent HCC after curative-intent surgery.

Hepatocellular carcinoma (HCC) is often recognized as an inflammation-linked cancer, which possesses an immunosuppressive tumor microenvironment. Curative treatments such as surgical resection, liver transplantation, and percutaneous ablation are mainly applicable in the early stage and demonstrate significant improvement of survival rate in most patients. However, 70-80% of patients report HCC recurrence within 5 years of curative treatment, representing an important clinical issue. However, there is no effective recurrence marker after surgical and locoregional therapies, thus, tumor size, number, and histological features such as cancer cell differentiation are often considered as risk factors for HCC recurrence. Host immunity plays a critical role in regulating carcinogenesis, and the immune microenvironment characterized by its composition, functional status, and density undergoes significant alterations in each stage of cancer progression. Recent studies reported that analysis of immune contexture could yield valuable information regarding the treatment response, prognosis and recurrence. This review emphasizes the prognostic value of tumors associated with immune factors in HCC recurrence after curative treatment. In particular, we review the immune landscape and immunological factors contributing to early-stage HCC recurrence, and discuss the immunotherapeutic interventions to prevent tumor recurrence following curative treatments.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the fifth leading cause of cancer death worldwide and the third leading cause of all diseases worldwide. Liver transplantation, surgical resection and ablation are the three main curative treatments for HCC. Liver transplantation is the optimal treatment option for HCC, but its usage is limited by the shortage of liver sources. Surgical resection is considered the first choice for early-stage HCC, but it does not apply to patients with poor liver function. Therefore, more and more doctors choose ablation for HCC. However, intrahepatic recurrence occurs in up to 70% patients within 5 years after initial treatment. For patients with oligo recurrence after primary treatment, repeated resection and local ablation are both alternative. Only 20% patients with recurrent HCC (rHCC) indicate repeated surgical resection because of limitations in liver function, tumor location and intraperitoneal adhesions. Local ablation has become an option for the waiting period when liver transplantation is unavailable. For patients with intrahepatic recurrence after liver transplantation, local ablation can reduce the tumor burden and prepare them for liver transplantation. This review systematically describes the various ablation treatments for rHCC, including radiofrequency ablation, microwave ablation, laser ablation, high-intensity focused ultrasound ablation, cryablation, irreversible electroporation, percutaneous ethanol injection, and the combination of ablation and other treatment modalities.

To estimate the potential of preoperative MR imaging features and clinical parameters in the risk stratification of patients with solitary hepatocellular carcinoma (HCC) ≤ 5 cm without microvascular invasion (MVI) after hepatectomy.

The study enrolled 166 patients with histopathological confirmed MVI-negative HCC retrospectively. The MR imaging features were evaluated by two radiologists independently. The risk factors associated with recurrence-free survival (RFS) were identified by univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression analysis. A predictive nomogram was developed based on these risk factors, and the performance was tested in the validation cohort. The RFS was analyzed by using the Kaplan-Meier survival curves and log-rank test.

Among the 166 patients with solitary MVI-negative HCC, 86 patients presented with postoperative recurrence. Multivariate Cox regression analysis indicated that cirrhosis, tumor size, hepatitis, albumin, arterial phase hyperenhancement (APHE), washout, and mosaic architecture were risk factors associated with poor RFS and then incorporated into the nomogram. The nomogram achieved good performance with C-index values of 0.713 and 0.707 in the development and validation cohorts, respectively. Furthermore, patients were stratified into high- and low-risk subgroups, and significant prognostic differences were found between the different subgroups in both cohorts (p < 0.001 and p = 0.024, respectively).

The nomogram incorporated preoperative MR imaging features, and clinical parameters can be a simple and reliable tool for predicting RFS and achieving risk stratification in patients with solitary MVI-negative HCC.

• Application of preoperative MR imaging features and clinical parameters can effectively predict RFS in patients with solitary MVI-negative HCC. • Risk factors including cirrhosis, tumor size, hepatitis, albumin, APHE, washout, and mosaic architecture were associated with worse prognosis in patients with solitary MVI-negative HCC. • Based on the nomogram incorporating these risk factors, the MVI-negative HCC patients could be stratified into two subgroups with significant different prognoses.

To investigate the value of pre-operative gadoxetate disodium (Gd-EOB-DTPA) enhanced MRI predicting early post-operative recurrence (< 2 years) of hepatocellular carcinoma (HCC) with different degrees of pathological differentiation.

Retrospective analysis of pre-operative MR imaging features of 177 patients diagnosed as suffering from HCC and that underwent radical resection. Multivariate logistic regression assessment was adopted to assess predictors for HCC recurrence with different degrees of pathological differentiation. The area under the curve (AUC) of receiver operating characteristics (ROC) was utilized to assess the diagnostic efficacy of the predictors.

Among the 177 patients, 155 (87.5%) were males, 22 (12.5%) were females; the mean age was 49.97 ± 10.71 years. Among the predictors of early post-operative recurrence of highly-differentiated HCC were an unsmooth tumor margin and an incomplete/without tumor capsule (p = 0.037 and 0.033, respectively) whereas those of early post-operative recurrence of moderately-differentiated HCC were incomplete/without tumor capsule, peritumoral enhancement along with peritumoral hypointensity (p = 0.006, 0.046 and 0.004, respectively). The predictors of early post-operative recurrence of poorly-differentiated HCC were peritumoral enhancement, peritumoral hypointensity, and tumor thrombosis (p = 0.033, 0.006 and 0.021, respectively). The AUCs of the multi-predictor diagnosis of early post-operative recurrence of highly-, moderately-, and poorly-differentiated HCC were 0.841, 0.873, and 0.875, respectively. The AUCs of the multi-predictor diagnosis were each higher than for those predicted separately.

The imaging parameters for predicting early post-operative recurrence of HCC with different degrees of pathological differentiation were different and combining these predictors can improve the diagnostic efficacy of early post-operative HCC recurrence.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies, recurrence rates remain high. In contrast to first-line treatment for HCC, which relies on several factors, including clinical staging, tumor burden, and liver function, there is no consensus or general treatment recommendations for recurrent HCC (R-HCC). Locoregional therapies include a spectrum of minimally invasive liver-directed treatments which can be used as either curative or neoadjuvant therapy for HCC. Herein, we provide a comprehensive review of recent evidence using salvage loco-regional therapies for R-HCC after failed curative-intent.

Surgical resection is the optimal treatment for HCC, despite a high risk of recurrence. Few data are available on patient’s survival after resection. This is a retrospective study of tumor recurrence occurring after hepatectomy for HCC from 2000 to 2016. Univariate and multivariate analyses were performed to identify prognostic factors of survival after recurrence (SAR). Among 387 patients, 226 recurred (58.4%) with a median SAR of 26 months. Curative treatments (liver transplantation, repeat hepatectomy, thermal ablation) were performed for 44.7% of patients. Independent prognostic factors for SAR were micro-vascular invasion on the primary surgical specimen, size of the initial tumor >5 cm, preoperative AFP, albumin and platelet levels, male gender, number, size and localization of tumors at recurrence, time to recurrence, Child−Pugh score and treatment at recurrence. In subgroup analysis, early recurrence (46%) was associated with a decrease in SAR, by contrast with late recurrence. However, the overall survival (OS) of patients with early recurrence and curative treatment did not significantly differ from that of non-recurring patients. For late recurrence, OS did not significantly differ from that of non-recurring patients, regardless of the proposed treatment. Aggressive and repeat treatments are therefore key to improve prognosis of patients with HCC.